Oral compositions for the treatment of cellulite

ABSTRACT

The present invention relates to oral pharmaceutical and cosmetic compositions for the treatment of cellulite containing  Vitis vinifera  extracts,  Centella asiatica  triterpenes and dimeric  Ginkgo biloba  flavonoids, in the free form or complexed with phospholipids.

The present invention relates to oral pharmaceutical and cosmeticcompositions containing ingredients of vegetable origin for thetreatment of cellulite.

More particularly, the present invention relates to pharmaceutical andcosmetic oral compositions for the treatment of cellulite containingVitis vinifera extracts, dimeric Ginkgo biloba flavonoids and Centellaasiatica triterpenes as the active ingredients.

According to the present invention, the active ingredients are in thefree form or complexed with phospholipids.

Cellulite affects a remarkable and increasing percentage of the westernpopulation, especially women, including many adult women with normalbody weight not affected by obesity. Cellulite is related to a conditionof panniculopathy, characterized by poor peripheral circulation, oedema,fibrosis and altered lipocytes metabolism, and an ideal treatment shouldtake into account all these aspects.

A number of pharmaceutical or cosmetic compositions for the treatment ofcellulite are presently available on the market: they are generallybased on active principles of vegetable origin, such as ivy,horse-chestnut or kola tree (Centella asiatica) extracts, caffeine,beta-adrenergic stimulants, methylxanthines and the like. However, noneof them has proved really effective so far and the improvements areoften due to the diet regimen generally associated with the use of thecompositions, rather than to the compositions themselves.

It has now been found that oral pharmaceutical and/or cosmeticcompositions containing a combination of active principles of vegetableorigin, which are object of the present invention, allow to obtainoptimal results in the treatment of cellulite, significantly reducingthe deposits of subcutaneous fat and “orange peel” skin, thanks to thecombination of the different activity of the various components, whichexert antioedema, antiphosphodiesterasis and vasokinetic activity, andpromote collagen production. The compositions of the invention have alsoproved effective in the treatment of venous insufficiency of the lowerlimbs.

All the active principles of the compositions of the invention are knownand used in pharmaceuticals and/or in cosmetics; however, it should benoted that the compositions show a synergistic effect and that theactivity of the single actives used separately is by far lower than thatof the actives used in combination.

The compositions of the present invention can contain from 10 to 500 mgper dose unit of Vitis vinifera standardized extracts, from 10 to 500 mgof dimeric Ginkgo biloba flavonoids and from 10 to 500 mg of Centellaasiatica or an equivalent amount of the corresponding phospholipidcomplexes.

Components a)-c) in the free form are commercially available.

Phospholipid complexes of Vitis vinifera standardized extract (alsoreferred to as “components a”) are disclosed in European Patent 275.224.Said extract, consisting of the poliphenols fraction contained in Vitisvinifera seeds, contains gallic acid, catechin and epicatechin monomers,dimers, trimers, tetramers, pentamers, hexamers and eptamers in the freeform or esterified with gallic acid.

In vitro and in vivo studies have demonstrated the high antioxidantactivity of the extract (from 10 to 200 times higher than that ofvitamin E, depending on the experimental model), which allows toeliminate the most reactive radical species and counteract their harmfuleffects. Moreover, the extract is able to inhibit xanthine-oxidase andchelate Cu⁺⁺ and Fe⁺⁺⁺, thus preventing enzyme-catalysed production offree radicals in tissues. Last, the Vitis vinifera extract inhibitscollagenase and other proteases, thereby protecting the connectivetissue and the skin from the noxious action of proteolytic enzymesreleased upon UV irradiation and in the course of inflammatory responsesin the skin; moreover, the extract has selective affinity for the skinand circulatory structures, such as microvessells and capillaries, thusalso exerting a protective action on the circulatory apparatus.

The complexes of dimeric Ginkgo biloba flavonoids with phospholipids(also referred to as “components b”), disclosed in EP 0 275 005, havethe same activity of Ginkgo biloba flavones dimers in the free form, butinduce a more prolonged release of the active principles and have abetter bioavailability. Ginkgo biloba flavonoids dimers are extremelypotent vasoactive agents due the fact that they inhibit the release ofhistamine and cAMP phosphodiesterase from mast cells. In particular, theinhibition of cAMP phosphodiesterase causes an increase of cAMP levels;since cAMP is able to activate lipocytes metabolism, these complexesexert a lipolytic action and improve microvascular perfusion andcutaneous trophism.

Phospholipid complexes of Centella asiatica standardized extract (alsoreferred to as “components c”) are disclosed in EP 0 283 713. Thisextract consists of a 4:3:3 mixture of three different molecules endowedwith high activity on collagen metabolism: asiaticoside, asiatic acidand madecassic acid. These molecules improve the fibroblasts uptake ofamino acids, mainly L-proline and L-hydroxyproline, which are the mostimportant amino acids in collagen structure, both from the qualitativeand quantitative standpoint. An improved collagen biosynthesis involvesa faster replacement of degraded old fibres with new ones.

The compositions of the present invention will be administered orally,in the form of suitable formulations, either liquid (such as syrups,solutions, suspensions) or solid (such as tablets, sugar-coated pills,capsules, chewable tablets). The formulations will be prepared accordingto conventional methods, such as those disclosed in “Remington'sPharmaceutical Handbook”, Mack Publishing Co., New York, USA, usingsuitable excipients.

Examples of compositions according to the invention are reportedhereinbelow.

EXAMPLE I Tablet

Phospholipids complex Vitis vinifera extract 240 mg  Phospholipidcomplex of dimeric Ginkgo biloba flavonoids 100 mg  Phospholipid complexof Centella asiatica triterpenes 60 mg Sodium croscaramellose 28 mgSilicon dioxide  8 mg Talc  4 mg

EXAMPLE II

Vitis vinifera extract 150 mg Ginkgo biloba dimeric flavonoids 100 mgCentella asiatica triterpenes  10 mg Dihydrate dicalcium phosphate 150mg Microcristalline cellulose 100 mg Croscaramellose sodium  28 mgSilicon dioxide  8 mg Magnesium stearate  9 mg Talc  3 mg

1. Oral compositions containing: a) Vitis vinifera standardized extractor a complex thereof with phospholipids; b) dimeric Ginkgo bilobaflavonoids or complexes thereof with phospholipids; c) Centella asiaticaor complexes thereof with phospholipids, in admixture with conventionalexcipients and carriers.
 2. Compositions as claimed in claim 1, in whichthe components a)-c) are in the free form.
 3. Compositions as claimed inclaim 1, in which the components a)-c) are in the form of complexes withphospholipids.
 4. Use of a combination of: a) Vitis viniferastandardized extract or a complex thereof with phospholipids; b) dimericGinkgo biloba flavonoids or complexes thereof with phospholipids and c)Centella asiatica or complexes thereof with phospholipids for thepreparation of oral pharmaceutical and cosmetic compositions for thetreatment of cellulite.
 5. Use of a combination of: a) Vitis viniferastandardized extract or complex thereof with phospholipids; b) dimericGinkgo biloba flavonoids or complexes thereof with phospholipids; c)Centella asiatica or complexes thereof with phospholipids for thetreatment of venous insufficiency of the lower limbs.
 6. Use of thecompositions of claim 1 for the treatment of cellulite.